High-dose Grid radiotherapy, or sometimes termed spatially-fractionated Grid radiotherapy (SFGRT), was first introduced in the early 1930's. It has remained a less frequently used treatment modality since its inception and practice. Early applications of high-dose Grid radiotherapy used two-dimensional (2D) Grid fields, typically with orthovoltage beams allowing spatially alternated dose distributions. The Grids were usually composed of open/shield circular or square shapes ranging in size from 0.5 cm to 1.5 cm. The application was mainly for the treatment of advanced bulky tumors. It was proposed that such treatment technique permits higher dose delivery with acceptable skin toxicity because highly exposed skin regions are surrounded by undamaged skin resulting in improved repair to those exposed skin regions. With this technique, only a portion of the tumor volume receives therapeutic dose.
Although relatively small numbers of patients have received Grid treatment either with orthovoltage or more recently with MV X-rays, significant and dramatic tumor regressions have been observed and reported even though Grid therapy, in contradistinction to conventional approaches, does not attempt to treat the total tumor volume with a rather uniform dose.
Recent research in radiobiology has brought forth newly revealed biological insights. These include the bystander effect within the Grid irradiated tumor volume that occurs in the tumor cells that fall directly under shielded regions (low-dose regions) of the Grid. Bystander factors such as Tumor Necrosis Factor-α (TNF-α), TNF-Related Apoptosis-Inducing Ligand (TRAIL), and Ceramide are induced in cells that are under the open field of the high-dose Grid areas and are hypothesized to be responsible for initiating the cell death cascade both in the epithelial and endothelial compartments of the tumor micro-environment. In addition to the bystander effect within the Grid irradiated tumor, robust abscopal effect in distant tumors or metastatic lesions that are not irradiated or treated has been reported. This data from radiobiology research conducted strongly suggests that Grid therapy induces a more rapid rate of tumor cell apoptosis in bulky, hypoxic, tumors than conventional dosimetric approaches. It is hypothesized from the research results that induction high-dose Grid radiotherapy would enhance the therapeutic outcome of subsequent chemotherapy or conventional radiation therapy.